Pharmacokinetic disposition of pethidine under tolerance

Under tolerance, evoked by multiple doses of pethidine (PD), the serum and brain tissue content of PD was related to diminished analgesic activity. Even though in tolerant rats no enhancement of PD biotransformation in the liver could be recognized (as followed by the measurement of hepatic esterase and N-demethylase activity), the amounts of both PD and nor-PD excreted in urine were increased under tolerance. The authors conclude that the faster disposition of PD may contribute to the development of tolerance.     

Structure elucidation of the core octasaccharide from Citrobacter PCM 1487 with the aid of 500-MHz, two-dimensional phase-sensitive correlated, relayed-coherence transfer, double-quantum, triple-quantum filtered, and N.O.E. H-n.m.r. spectra

The main features of the primary structure of the octasaccharide, - -Glcp-(1→2)-- -Glcp-(1→2)-[- -GalpNAc- (1→3)]-- -Galp-(1→3)-- -Glcp-(1→3)-[- -Hepp-(1→7)]-- -Hepp-(1→3)-- -Hep, have been determined in the ab initio manner by ¹H-n.m.r. spectroscopy without resorting to biochemical methods of analysis. Several nontypical interresidue n.O.e. values point to a preferred solution conformation of the molecule.     

Effect of repeated treatment with desipramine in the behavioral "despair" test in rats: antagonism by "atypical" but not "classical" neuroleptics or antiadrenergic drugs

A 7-day treatment with 20 mg/kg/day desipramine reduced the immobility time in the behavioral "despair" test in rats. The effect of DMI was antagonized by sulpiride (100 mg/kg i.p.), metoclopramide (20 mg/kg i.p.) and clopazine (20 mg/kg i.p.) but not by haloperidol (0.5 mg/kg i.p.) or chlorpromazine (5 mg/kg i.p.). Alpha-adrenoreceptor blockers (prazosin 3 mg/kg s.c.; aceperone 10 mg/kg i.p.; azapetine 24 mg/kg s.c.; phentolamine 20 mg/kg i.p.), dl-propranolol (5 mg/kg i.p.) and clonidine (0.1 mg/kg i.p.) failed to modify the anti-immobility effect of DMI. The data suggest that a particular subtype of dopamine receptors is involved in the anti-immobility effect of a 7-day treatment with DMI in the behavioral "despair" test in rats.     

Tumor necrosis factor-alpha converting enzyme is processed by proprotein-convertases to its mature form which is degraded upon phorbol ester stimulation.

Tumor necrosis factor-alpha converting enzyme (TACE or ADAM17) is a member of the ADAM (a disintegrin and metalloproteinase) family of type I membrane proteins and mediates the ectodomain shedding of various membrane-anchored signaling and adhesion proteins. TACE is synthesized as an inactive zymogen, which is subsequently proteolytically processed to the catalytically active form. We have identified the proprotein-convertases PC7 and furin to be involved in maturation of TACE. This maturation is negatively influenced by the phorbol ester phorbol-12-myristate-13-acetate (PMA), which decreases the cellular amount of the mature form of TACE in PMA-treated HEK293 and SH-SY5Y cells. Furthermore, we found that stimulation of protein kinase C or protein kinase A signaling pathways did not influence long-term degradation of mature TACE. Interestingly, PMA treatment of furin-deficient LoVo cells did not affect the degradation of mature TACE. By examination of furin reconstituted LoVo cells we were able to exclude the possibility that PMA modulates furin activity. Moreover, the PMA dependent decrease of the mature enzyme form is specific for TACE, as the amount of mature ADAM10 was unaffected in PMA-treated HEK293 and SH-SY5Y cells. Our results indicate that the activation of TACE by the proprotein-convertases PC7 and furin is very similar to the maturation of ADAM10 although there is a significant difference in the cellular stability of the mature enzyme forms after phorbol ester treatment.     

Studies on the import and processing of the alternative oxidase precursor by isolated soybean mitochondria

Import of the synthetic precursor of the alternative oxidase from soybean was shown to be dependent on a membrane potential and ATP. The membrane potential in soybean mitochondria may be formed either by respiration through the cytochrome pathway, or through the alternative oxidase pathway with NAD⁺-linked substrates. Import of the alternative oxidase precursor in the presence of succinate as respiratory substrate was inhibited by KCN. Import in the presence of malate was insensitive to KCN and SHAM added separately, but was inhibited by KCN and SHAM added together (inhibitors of the cytochrome and alternative oxidases respectively). Import of the alternative oxidase was accompanied by processing of the precursor to a single 32 kDa product in both cotyledon and root mitochondria. This product had a different mobility than the two alternative oxidase bands detected by immunological means (34 and 36 kDa), suggesting that the enzyme had been modified in situ. When the cDNA clone of the alternative oxidase was modified by a single mutation (–2 Arg changed to –2 Gly), the processing of the precursor was inhibited.     

Familial translocation t(1p-;21q+) associated with Down's syndrome

Summary Familial occurrence of 1/21 translocation in connection with trisomy 21 was described. The possibilities of inheritance of further chromosome rearrangements arising during the gametogenesis of persons with this translocation were considered.     

Sterols and frost hardening of winter rape

Winter rape ( Brassica napus L., var. olifera cv. Górczanski) seedlings were exposed to hardening conditions and the content and composition of free sterols as well as the ratio of free sterols to total phospholipids were determined. There was a reduction in free sterol content in the leaves at the most advanced stage of hardening. The ratio of free sterol to total phospholipids was significantly reduced by hardening due to a decrease in the level of the former and an increase in that of the latter compounds. There was a negative correlation between this ratio and the temperature at which half of the seedlings died. Thus, adaptation of membranes to temperature takes place also at the level of sterol-phospholipid interactions. Exposing seedlings already hardened to freezing temperatures caused injury higher than 50%, and brought about a drastic increase in the level of free sterols and an elevation in the ratio of free sterols to phospholipids. The results are discussed in terms of a possible role of the molecular architecture of membranes in surviving at subzero temperatures.